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Belirsiz sitolojili tiroid nodüllerinde ince iğne aspirasyon biyopsisi yanlış negatifliğine etkili faktörler

Year 2023, Volume: 48 Issue: 2, 499 - 512, 02.07.2023
https://doi.org/10.17826/cumj.1253393

Abstract

Amaç: İnce iğne aspirasyon biyopsilerinin (İİAB) yanlış negatif sonuçları tiroid nodüllerine yaklaşımda en önemli sorunlardan biri olmaya devam etmektedir. Bu çalışmanın amacı, özellikle belirsiz sitolojili tiroid nodüllerinde İİAB'nin yanlış negatif sonuçlarını etkileyen faktörleri değerlendirmektir.
Gereç ve Yöntem: Ocak 2017 ile Ocak 2020 arasında İİAB yapılan ve ardından tiroidektomi kararı alınan tiroid nodüllü hastalar çalışmaya dahil edildi. TIRADS sınıflamasına uygun olarak şüpheli nodüllerden İİAB yapıldı. İİAB'ye göre "atipi/önemi belirsiz foliküler lezyon (AUS/FLUS)", "Non-diagnostik sitoloji (ND)" veya "Folliküler neoplazm/foliküler neoplazm için şüpheli (FN/SFN)" olan nodüller "Belirsiz sitoloji (IC)" olarak tanımlandı. Nodüller İİAB ve final patoloji uyumlarına göre iki gruba ayrıldı. Yalancı negatif İİAB saptanan nodüller Grup-1'e alınırken, doğru pozitif ve doğru negatif İİAB sonuçları Grup 2'ye alındı. Hastaların demografik ve klinik verileri, patolojik sonuçları ve genetik profilleri tüm hastalar ve IC grubu için ayrı ayrı istatistiksel olarak karşılaştırıldı.
Bulgular: 94 hastanın İİAB sonuçları ile final patoloji sonucları uyumsuz (Grup-1), 233 hastanın ise uyumlu bulundu (Grup-2). IC alt grubunda 95 hastanın 56'sı IC/Grup-1'de, 39'u ise IC/Grup-2'de yer aldı. Ekstratiroidal yayılım (%71.4 vs. %30.8), perinöral/lenfovasküler invazyon (%60.0 vs. %29.6), klasik varyant varlığında (%68.5 vs. 50.7%), non-enkapsüle tümörlerde (%67.9 vs. %50.0) ve multisentrik tümörlerde (%47.2 vs. %24.1) İİAB doğruluğu istatistiksel olarak anlamlı derecede yüksek saptandı. IC grubunda tiroidit varlığında (%75.0 vs. %49.2) ve yüksek serum Anti-TPO düzeylerinde (%60.0 vs. %30.7) İİAB yanlış negatifliği artmaktadır. Yüksek serum Nötrofil/Lenfosit Oranı (NLR) ve küçük tümör boyutu varlığı da özellikle IC grubu hastalarda İİAB'nin yanlış negatifliğini arttırmaktadır.
Sonuç: Ekstratiroidal yayılım, perinöral/lenfovasküler invazyon, non-enkapsüle tümör ve multisentrik tümörler gibi agresif seyir göstermesi beklenen tümörlerde ve klasik varyant tümörlerde İİAB'nin tanısal doğruluğu artmaktadır. Bununla beraber tiroidit varlığında, yüksek serum Anti-TPO düzeyleri ve yüksek NLR varlığında İİAB'nin yanlış negatif sonuçlarının arttığı akılda tutulmalıdır.

References

  • Jiang H, Tian Y, Yan W, Kong Y, Wang H, Wang A et .al. The prevalence of thyroid nodules and an analysis of related lifestyle factors in Beijing communities. Int J Environ Res Public Health. 2016;13:442.
  • Guth S, Theune U, Aberle J, Galach A, and Bamberger C. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest. 2009;39:699-706.
  • Frates MC, Benson CB, Doubilet PM, Kunreuther E, Contreras M, Cibas ES et al. Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography. J Clin Endocrinol Metab. 2006;91:3411-7.
  • Yang J, Schnadig V, Logrono R, Wasserman PG. Fine‐needle aspiration of thyroid nodules: a study of 4703 patients with histologic and clinical correlations. Cancer. 2007;111:306-15.
  • Baloch ZW, Sack MJ, Hu GH, Livolsi VA, and Gupta PK. Fine-needle aspiration of thyroid: an institutional experience. Thyroid. 1998;8:565-9.
  • Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda system for reporting thyroid cytopathology: a meta‐analysis. Acta Cytol. 2012; 56:333-9.
  • Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26:1-133.
  • Yim Y, Baek JH. Core needle biopsy in the management of thyroid nodules with an indeterminate fine-needle aspiration report. Gland Surg. 2019;8:77-85
  • Trimboli P, Virili C, Romanelli F. Galectin-3 performance in histologic a cytologic assessment of thyroid nodules: a systematic review and meta-analysis. Int J Mol Sci. 2017;18:1756.
  • Trimboli P, Fulciniti F, Zilioli V. Accuracy of international ultrasound risk stratification systems in thyroid lesions cytologically classified as indeterminate. Diagn Cytopathol. 2017;45:113-7.
  • Hoperia V, Larin A, Jensen K, Bauer A, Vasko V. Thyroid fine needle aspiration biopsies in children: study of cytological-histological correlation and immunostaining with thyroid peroxidase monoclonal antibodies. Int J Pediatr Endocrinol. 2010;690108:1-5.
  • AIUM practice guideline for the performance of a thyroid and parathyroid ultrasound examination. J Ultrasound Med. 2013;32:1319-29.
  • Grani G, Sponziello M, Pecce V, Ramundo V, Durante C. Contemporary thyroid nodule evaluation and management. J Clin Endocrinol Metab. 2020;105:2869-83.
  • Kumbhar SS, O’Malley RB, Robinson TJ, Maximin S, Lalwani N, Byrd DR et al. Why thyroid surgeons are frustrated with radiologists: lessons learned from pre-andpostoperative US Radiographics. 2016;36:2141-53.
  • Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, Hegedüs L et al. AACE/ACE/AME task force on thyroid nodules American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules–2016 update. Endocr Pract. 2016;22:622-39.
  • Russ G, Bonnema SJ, Erdogan MF, Durante C, Ngu R, Leenhardt L. European Thyroid Association guidelines for ultrasound malignancy risk stratification of thyroid nodules in adults: the EU-TIRADS. Eur Thyroid J. 2017;6:225-37.
  • Shin JH, Baek JH, Chung J, Ha EJ, Kim JH, Lee YH et al.; Korean Society of Thyroid Radiology (KSThR) and Korean Society of Radiology ultrasonography diagnosis and imaging-based management of thyroid nodules: revised Korean Society of Thyroid Radiology consensus statement and recommendations. Korean J Radiol. 2016;17:370-95.
  • Todsen T, bennedbeak N, Kiss K, Hegedüs L. Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules. Head Neck. 2021;43:1009-13.
  • Bestepe N, Ozdemir D, Tam AA, Dellal FD, Kilicarslan A, Parlak O et al. Malignancy risk and false-negative rate of fine needle aspiration cytology in thyroid nodules ≥4.0 cm. Surgery. 2016;160:405-12.
  • McCoy KL, Jabbour N, Ogilvie JB, Ohori NP, Carty SE, Yim JH. The incidence of cancer and rate of false negative cytology in thyroid nodules greater than or equal to 4cm in size. Surgery. 2007;142:837-44.
  • McHenry CR, Huh ES, and Machekano RN. Is nodule size an independent predictor of thyroid malignancy? Surgery. 2008;144:1062-8.
  • Carillo JF, Frias-Mendivil M, Ochoa-Carrillo FJ, Ibarra M. Accuracy of fine-needle aspiration biopsy of thyroid combined with an evaluation of clinical and radiologic factors. Otolaryngol Head Neck Surg. 2000;122:917-21.
  • Kuru B, Gulcelik NE, Gulcelik MA, Dincer H. The false negative rate of fine-needle aspiration cytology for diagnosing thyroid carcinoma in thyroid nodules. Langenbecks Arch Surg. 2010;395:127-32.
  • Shrestha M, Crothers BA, Burch HB. The impact of thyroid nodule size on the risk of malignancy and accuracy of fine needle aspiration: A 10-year study from a single institution. Thyroid. 2012;22:1251-6.
  • Porterfield JR Jr, Grant CS, Dean DS, Thompson GB, Farley DR, Richards ML et al. Reliability of benign fine needle aspiration cytology of large thyroid nodules. Surgery. 2008;144:963-8.
  • Rosario PW, Salles DS, Bessa B, Purisch S. Low false-negative rate of cytology in thyroid nodules >4cm. Arq Bras Endocrinol Metab. 2009;53:1143-5.
  • Renshaw AA, Gould EW. Characteristics of false-negative thyroid fine-needle aspirates. Acta Cytol. 2018;62:12-18
  • Ali SZ, Cibas ES. Editors. The Bethesda system for reporting thyroid cytopathology. definitions, criteria, and explanatory notes. 2nd ed. New York: Wiley. 2017.
  • Roh MH, Jo VY, Stelow EB, Faquin WC, Zou KH, Alexander EK et al. The predictive value of the fine-needle aspiration diagnosis "suspicious for a follicular neoplasm, hurthle cell type" in patients with Hashimoto thyroiditis. Am J Clin Pathol. 2011;135:139-45.
  • Belfiore A, La Rosa GL. Fine-needle aspiration biopsy of the thyroid. Endocrinol Metab Clin North Am. 2001;30:361-400.
  • Ari A, Gunver F. Comparison of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with thyroiditis and papillary tumors. J Int Med Res. 2019;47:2077-83.
  • Shrestha RT, Evasovich MR, Amin K, Radulescu A, Sanghvi TS, Nelson AC et al. Correlation between histological diagnosis and mutational panel testing of thyroid nodules: A Two-year institutional experience. Thyroid. 2016;26:1068-76.

Factors affecting the false negativity of fine-needle aspiration biopsy in thyroid nodules with indeterminate cytology

Year 2023, Volume: 48 Issue: 2, 499 - 512, 02.07.2023
https://doi.org/10.17826/cumj.1253393

Abstract

Purpose: False negative results of fine needle aspiration biopsies (FNAB) remain one of the most important problems in the management of thyroid nodules. The aim of this study was to evaluate the factors affecting the false negative results of FNAB, especially in thyroid nodules with indeterminate cytology.
Materials and Methods: Patients with thyroid nodules who underwent FNAB and subsequent thyroidectomy between January 2017 and January 2020 were included in the study. FNAB was performed on suspicious nodules according to the TIRADS classification. Nodules with "atypia/follicular lesion of undetermined significance (AUS/FLUS)", "non-diagnostic (ND)" cytology or "follicular neoplasm/suspicious for follicular neoplasm (FN/SFN)" according to FNAB were defined as "indeterminate cytology (IC)". Nodules were analyzed in two groups. Nodules with false negative FNAB were included in Group-1, while nodules with true positive and true negative FNAB were included in Group-2. Demographic and clinical data, pathologic results and genetic profiles of the patients were statistically compared for all patients and IC group separately.
Results: The results of FNAB and final pathology were discordant in 94 patients (Group-1) and concordant in 233 patients (Group-2). In the IC subgroup, 56 of 95 patients were in IC/Group-1 and 39 patients were in IC/Group-2. The accuracy of FNAB was statistically significantly higher in the presence of extrathyroidal extension (71.4% vs. 30.8%), perineural/lymphovascular invasion (60.0% vs. 29.6%), classical variants (68.5% vs. 50.7%), non-encapsulated tumors (67.9% vs. 50.0%) and multicentricity (47.2% vs. 24.1%). In the IC group, the presence of thyroiditis (75.0% vs. 49.2%) and high serum Anti-TPO levels (60.0% vs. 30.7%) increased the rate of false negativity on FNAB. High serum Neutrophil to Lymphocyte Ratio (NLR) and small tumor size also increase the false negativity of FNAB, especially in IC group patients.
Conclusion: The diagnostic accuracy of FNAB is increased in classical variant tumors and in tumors expected to be aggressive due to presence of extra-thyroidal extension, perineural/lymphovascular invasion, non-encapsulated tumors and multicentricity. It should be kept in mind that the false negative results of FNAB increase in the presence of thyroiditis, high level of serum anti-TPO and high level of NLR.

References

  • Jiang H, Tian Y, Yan W, Kong Y, Wang H, Wang A et .al. The prevalence of thyroid nodules and an analysis of related lifestyle factors in Beijing communities. Int J Environ Res Public Health. 2016;13:442.
  • Guth S, Theune U, Aberle J, Galach A, and Bamberger C. Very high prevalence of thyroid nodules detected by high frequency (13 MHz) ultrasound examination. Eur J Clin Invest. 2009;39:699-706.
  • Frates MC, Benson CB, Doubilet PM, Kunreuther E, Contreras M, Cibas ES et al. Prevalence and distribution of carcinoma in patients with solitary and multiple thyroid nodules on sonography. J Clin Endocrinol Metab. 2006;91:3411-7.
  • Yang J, Schnadig V, Logrono R, Wasserman PG. Fine‐needle aspiration of thyroid nodules: a study of 4703 patients with histologic and clinical correlations. Cancer. 2007;111:306-15.
  • Baloch ZW, Sack MJ, Hu GH, Livolsi VA, and Gupta PK. Fine-needle aspiration of thyroid: an institutional experience. Thyroid. 1998;8:565-9.
  • Bongiovanni M, Spitale A, Faquin WC, Mazzucchelli L, Baloch ZW. The Bethesda system for reporting thyroid cytopathology: a meta‐analysis. Acta Cytol. 2012; 56:333-9.
  • Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26:1-133.
  • Yim Y, Baek JH. Core needle biopsy in the management of thyroid nodules with an indeterminate fine-needle aspiration report. Gland Surg. 2019;8:77-85
  • Trimboli P, Virili C, Romanelli F. Galectin-3 performance in histologic a cytologic assessment of thyroid nodules: a systematic review and meta-analysis. Int J Mol Sci. 2017;18:1756.
  • Trimboli P, Fulciniti F, Zilioli V. Accuracy of international ultrasound risk stratification systems in thyroid lesions cytologically classified as indeterminate. Diagn Cytopathol. 2017;45:113-7.
  • Hoperia V, Larin A, Jensen K, Bauer A, Vasko V. Thyroid fine needle aspiration biopsies in children: study of cytological-histological correlation and immunostaining with thyroid peroxidase monoclonal antibodies. Int J Pediatr Endocrinol. 2010;690108:1-5.
  • AIUM practice guideline for the performance of a thyroid and parathyroid ultrasound examination. J Ultrasound Med. 2013;32:1319-29.
  • Grani G, Sponziello M, Pecce V, Ramundo V, Durante C. Contemporary thyroid nodule evaluation and management. J Clin Endocrinol Metab. 2020;105:2869-83.
  • Kumbhar SS, O’Malley RB, Robinson TJ, Maximin S, Lalwani N, Byrd DR et al. Why thyroid surgeons are frustrated with radiologists: lessons learned from pre-andpostoperative US Radiographics. 2016;36:2141-53.
  • Gharib H, Papini E, Garber JR, Duick DS, Harrell RM, Hegedüs L et al. AACE/ACE/AME task force on thyroid nodules American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazione Medici Endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules–2016 update. Endocr Pract. 2016;22:622-39.
  • Russ G, Bonnema SJ, Erdogan MF, Durante C, Ngu R, Leenhardt L. European Thyroid Association guidelines for ultrasound malignancy risk stratification of thyroid nodules in adults: the EU-TIRADS. Eur Thyroid J. 2017;6:225-37.
  • Shin JH, Baek JH, Chung J, Ha EJ, Kim JH, Lee YH et al.; Korean Society of Thyroid Radiology (KSThR) and Korean Society of Radiology ultrasonography diagnosis and imaging-based management of thyroid nodules: revised Korean Society of Thyroid Radiology consensus statement and recommendations. Korean J Radiol. 2016;17:370-95.
  • Todsen T, bennedbeak N, Kiss K, Hegedüs L. Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules. Head Neck. 2021;43:1009-13.
  • Bestepe N, Ozdemir D, Tam AA, Dellal FD, Kilicarslan A, Parlak O et al. Malignancy risk and false-negative rate of fine needle aspiration cytology in thyroid nodules ≥4.0 cm. Surgery. 2016;160:405-12.
  • McCoy KL, Jabbour N, Ogilvie JB, Ohori NP, Carty SE, Yim JH. The incidence of cancer and rate of false negative cytology in thyroid nodules greater than or equal to 4cm in size. Surgery. 2007;142:837-44.
  • McHenry CR, Huh ES, and Machekano RN. Is nodule size an independent predictor of thyroid malignancy? Surgery. 2008;144:1062-8.
  • Carillo JF, Frias-Mendivil M, Ochoa-Carrillo FJ, Ibarra M. Accuracy of fine-needle aspiration biopsy of thyroid combined with an evaluation of clinical and radiologic factors. Otolaryngol Head Neck Surg. 2000;122:917-21.
  • Kuru B, Gulcelik NE, Gulcelik MA, Dincer H. The false negative rate of fine-needle aspiration cytology for diagnosing thyroid carcinoma in thyroid nodules. Langenbecks Arch Surg. 2010;395:127-32.
  • Shrestha M, Crothers BA, Burch HB. The impact of thyroid nodule size on the risk of malignancy and accuracy of fine needle aspiration: A 10-year study from a single institution. Thyroid. 2012;22:1251-6.
  • Porterfield JR Jr, Grant CS, Dean DS, Thompson GB, Farley DR, Richards ML et al. Reliability of benign fine needle aspiration cytology of large thyroid nodules. Surgery. 2008;144:963-8.
  • Rosario PW, Salles DS, Bessa B, Purisch S. Low false-negative rate of cytology in thyroid nodules >4cm. Arq Bras Endocrinol Metab. 2009;53:1143-5.
  • Renshaw AA, Gould EW. Characteristics of false-negative thyroid fine-needle aspirates. Acta Cytol. 2018;62:12-18
  • Ali SZ, Cibas ES. Editors. The Bethesda system for reporting thyroid cytopathology. definitions, criteria, and explanatory notes. 2nd ed. New York: Wiley. 2017.
  • Roh MH, Jo VY, Stelow EB, Faquin WC, Zou KH, Alexander EK et al. The predictive value of the fine-needle aspiration diagnosis "suspicious for a follicular neoplasm, hurthle cell type" in patients with Hashimoto thyroiditis. Am J Clin Pathol. 2011;135:139-45.
  • Belfiore A, La Rosa GL. Fine-needle aspiration biopsy of the thyroid. Endocrinol Metab Clin North Am. 2001;30:361-400.
  • Ari A, Gunver F. Comparison of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with thyroiditis and papillary tumors. J Int Med Res. 2019;47:2077-83.
  • Shrestha RT, Evasovich MR, Amin K, Radulescu A, Sanghvi TS, Nelson AC et al. Correlation between histological diagnosis and mutational panel testing of thyroid nodules: A Two-year institutional experience. Thyroid. 2016;26:1068-76.
There are 32 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research
Authors

İbrahim Ali Özemir 0000-0001-8693-9358

Early Pub Date July 10, 2023
Publication Date July 2, 2023
Acceptance Date June 4, 2023
Published in Issue Year 2023 Volume: 48 Issue: 2

Cite

MLA Özemir, İbrahim Ali. “Factors Affecting the False Negativity of Fine-Needle Aspiration Biopsy in Thyroid Nodules With Indeterminate Cytology”. Cukurova Medical Journal, vol. 48, no. 2, 2023, pp. 499-12, doi:10.17826/cumj.1253393.